ORPHA:572798
WARS2-related combined oxidative phosphorylation defect
Also known as: Mitochondrial tryptophanyl-tRNA synthetase deficiency
Publications
6,128
Trials
0
Interventional, condition-specific
Researchers
63
Distinct authors in sample
Gene link
WARS2
Strong
Readiness
3/6
Stages with a signal
Clinical definition (Orphanet)
A rare oxidative phosphorylation disorder characterized by a spectrum of three main clinical phenotypes comprising a severe with early fatal lactic , a more protracted course with early-onset , motor weakness, extrapyramidal signs, and with or without , and a with normal early development and Parkinson-like symptoms starting around the age of one year. Additional, variably reported, signs and symptoms include , optic anomalies, , and abnormal brain MRI findings, among others. Deficiencies in oxidative phosphorylation enzymes are inconsistent.
How rare: <1 / 1 000 000 — fewer than one in a million. In a city the size of Kolkata, that might mean on the order of fifteen people.
Cross-references
Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.
- MONDO:0060578
- OMIM:617710
- UMLS:C4540192
Additional Mondo synonyms (2)
mitochondrial tryptophanyl-tRNA synthetase deficiency · neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures
Research stages
Trial readiness signals
Where this condition sits on an open-data research pipeline — not how close a treatment is, and not medical advice. Empty stages often mean “not in these databases under this Mondo ID,” not “impossible.”
3/6 stages with a signal
No matched interventional trial; the gene is known and literature exists — preclinical or natural-history work may still be the practical next step.
- Gene identifiedPresent
Strong — WARS2
- LiteraturePresent
6,128 matched papers (3,308 in last 10 years) Source
- Phenotype characterisedPresent
99 HPO annotations (e.g. Intellectual disability; Global developmental delay; Floppy infant) Source
- Animal modelNot found
No Alliance genotype “model of” associations via Monarch for these Mondo IDs
- Orphan designationNot found
No FDA or EMA orphan-drug designation matched this disease via UMLS or preferred name Source
- Interventional trialNot found
No matched interventional trial under our ClinicalTrials.gov rules
Biology
Genes and phenotypes
Gene–disease validity from GenCC, plus phenotypes and animal models joined from Monarch Initiative via Mondo ID — not a clinical diagnosis aid.
Do we know what causes it?
Yes — we know a specific gene responsible (WARS2).
GenCC classification: Strong.
Phenotypes (Monarch / HPO)
99
Associated phenotypes · MONDO:0060578
- Intellectual disability
- Global developmental delay
- Floppy infant
- Abnormality of movement
- Seizure
Showing 5 of 99 — open Monarch for the full list.
Animal models (Monarch / Alliance)
None returned for this Mondo ID. Empty here is not proof that no model organism work exists under another name or gene.
Monarch fetch 2026-07-29
Therapies
Designations, candidates, and chemicals
FDA OOPD and EMA orphan designations, Open Targets clinical candidates, and CTD chemical associations via MyDisease.info. These never change the interventional-trial headline.
Orphan designation (FDA · EMA)
No designation matched this disease via UMLS or preferred name on the FDA OOPD mirror or EMA orphan register. Absence here is not proof that none exists under another wording.
Open Targets candidates
No drugs or clinical candidates returned for this Mondo ID on Open Targets.
CTD chemicals (MyDisease.info)
No CTD chemical associations returned for this Mondo ID.
Literature
Is anyone studying this?
6,128
6,128 papers — among the better-studied rare conditions, though still a fraction of common-disease literature (breast cancer: over 700,000). Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=3967) is 59.
6,128 papers since the earliest indexed year in this search — median last-10-year count for a rare disease in this dataset is 59 (publications denominator n=3967).
3,308 in the last 10 years · low confidence
Phrase hits: 13 · MeSH hits: 0
Who's working on it?
63
Distinct author names in 13 sampled papers — named people below.
Who's working on it?
No interventional trial matched this name; these authors publish on it in the sampled literature — a practical starting point for contact.
- 01Jones K2 papers · 2020
1 Neurology Division, Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Papers in Europe PMC - 02Kozenko M2 papers · 2020
2 Genetics Division, Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Papers in Europe PMC - 03Tarnopolsky M2 papers · 2020
3 Neuromuscular and Neurometabolics Division, Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Papers in Europe PMC - 04Baruffini E1 paper · 2021
Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 11/A, 43124 Parma, Italy.
Papers in Europe PMC - 05Calakos N1 paper · 2025
Department of Neurology, Duke University Medical Center, Durham, North Carolina, USA.
Papers in Europe PMC - 06Cavalcanti ARO1 paper · 2022
Department of Biology, Pomona College, Claremont, CA, United States.
Papers in Europe PMC - 07Ceccatelli Berti C1 paper · 2021
Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 11/A, 43124 Parma, Italy.
Papers in Europe PMC - 08Chen YH1 paper · 2023
Department of Pediatrics, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, Fujian, China.
Papers in Europe PMC - 09Chen ZH1 paper · 2023
Department of Pediatrics, The Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha, Hunan, China.
Papers in Europe PMC - 10Coller JM1 paper · 2019
Department of Genetics and Genome Sciences and Center for RNA Science and Therapeutics, Case Western Reserve University, Cleveland, Ohio 44106, USA; email: ashleigh.schaffer@case.edu.
Papers in Europe PMC
Clinical research
Is a treatment being tested?
0
interventional trials for this specific condition
No interventional trial testing a treatment matched this specific condition name on ClinicalTrials.gov (observational studies and pan-disease registries are listed separately when present).
Data as of 11 September 2026 · last trial check 11 September 2026
No matched interventional trials. This is true for 77.2% of diseases in the trials denominator (5501 of 7126). Here are the researchers publishing on it.
low confidence · 38.6th percentile (trials denominator)
Recruiting interventional trials
From the matched ClinicalTrials.gov set
No interventional trial testing a treatment was found for this specific condition name on ClinicalTrials.gov.
See who's working on it — people publishing on this disease are often the practical next contact when no trial is listed.
Other registries (secondary)
Broader net from EU CTIS, ISRCTN, and ICTRP when available — deduped against ClinicalTrials.gov IDs already counted above. Dual-model LLM relevance gates what we keep. These rows are not added to the interventional headline.
raw 34 · after dedupe 34 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 34 · dropped 0 · fetched 2026-07-30
Source notes: ictrp: Error: ICTRP public search unavailable (WHO portal is SPA-only; SOAP needs partnership). Tried: https://apps.who.int/tri
No secondary-registry studies passed dual-model relevance for this condition name (after dedupe).
Uncertain / not reviewed (34)
- ctis·2025-524367-20-00·Authorised, ongoing·An open-label, single-arm extension study to evaluate the long-term safety, tolerability, and efficacy of KL1333 (napazimone) in patients with primary mitochondrial disease
skipped — LLM skipped (--skip-llm)
- ctis·2025-521628-31-00·Authorised·A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Subcutaneous Nomlabofusp in Subjects with Friedreich’s Ataxia
skipped — LLM skipped (--skip-llm)
- ctis·2025-523881-26-00·Authorised, ongoing·Identification of mitochondrial biomarkers reflecting omaveloxolone treatment (in FA patients)
skipped — LLM skipped (--skip-llm)
- ctis·2025-523828-51-00·Authorised·IB1001-304: Effects of N-Acetyl-L-Leucine on CACNA1A Disorders: A Phase III, randomized, placebo-controlled, double-blind, crossover study
skipped — LLM skipped (--skip-llm)
- ctis·2025-524709-34-00·Authorised·MitOxyVit: Mitochondrial network modulation approach using hyperbaric oxygen (HBO) therapy and NNbUVB for treating vitiligo
skipped — LLM skipped (--skip-llm)
- ctis·2025-524343-13-00·Authorised·Pilot study of the efficacy of nicotinamide (vitamin B3) in Leber's hereditary optic neuropathy - NICOLHON
skipped — LLM skipped (--skip-llm)
- ctis·2025-524674-42-00·Authorised, ongoing·A Phase 2, Randomized, Double-blind, Placebo-Controlled, Single-Center Study to Assess the effects of SUL-238 on High Energy Phosphates with Magnetic Resonance Spectroscopy (31P-MRS) in patients with Early, untreated Parkinson’s Disease (“SHEPHERD” STUDY)
skipped — LLM skipped (--skip-llm)
- ctis·2025-522361-30-00·Authorised, recruiting·A Phase III, randomised, double-blind, placebo-controlled, parallel-group, pivotal trial to assess the efficacy and safety of sonlicromanol in adult subjects with a genetically confirmed mitochondrial DNA tRNALeu(UUR) m.3243A>G variant.
skipped — LLM skipped (--skip-llm)
- ctis·2025-523339-20-00·Authorised, ongoing·A dose-ranging randomized, open-label study evaluating the effect of bilateral intravitreal injection of GS010 at two dose levels on visual acuity and retinal mitochondrial activity in patients affected with ND4 Leber Hereditary Optic Neuropathy – The REVISE Study
skipped — LLM skipped (--skip-llm)
- ctis·2025-522719-40-00·Authorised, ongoing·GAIN-CTNNB1: A Phase I/II open-label trial to evaluate the safety, tolerability, and preliminary efficacy of a single intracerebroventricular administration of an AAV9-based gene replacement therapy in paediatric patients with CTNNB1 syndrome
skipped — LLM skipped (--skip-llm)
- ctis·2024-519637-32-00·Authorised·PANACEA : Effect of PrehAbilitation by NutritionAl supplementation with Cannabidiol on skeletal muscle mass and mitochondrial function in hEad and neck cAncer : a proof of concept controlled randomized trial
skipped — LLM skipped (--skip-llm)
- ctis·2024-514852-34-01·Authorised, recruiting·Prospective pilot study of L-dopa treatment in patients with a neurodevelopmental disorder linked to a pathogenic variant of the CTNNB1 gene
skipped — LLM skipped (--skip-llm)
- ctis·2024-519461-22-00·Authorised, ongoing·PHArmacoKinetics of methYLphenidate in adult patients with ADHD: comparison between patients with and without OBesity_PHACYLOB.
skipped — LLM skipped (--skip-llm)
- ctis·2024-517514-15-00·Expired·An open-label extension study evaluating the safety of zagociguat in participants with MELAS who completed TIS6463-203
skipped — LLM skipped (--skip-llm)
- ctis·2024-514804-14-00·Authorised, ongoing·HALT : Influence of Human Albumin supplementation on kidney dysfunction after Liver Transplantation
skipped — LLM skipped (--skip-llm)
- ctis·2024-516561-37-01·Authorised, ongoing·Control strategies and pharmacogenetic study for the personalized treatment of fatty liver associated with metabolic dysfunction in patients with prediabetes.
skipped — LLM skipped (--skip-llm)
- ctis·2023-506723-28-00·Cancelled·A Multi-Center, Randomized, Single-Blind, Placebo-Controlled Study to Assess the Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral TTI-0102 for Treatment of Patients with Mitochondrial encephalomyopathy, lactic acidosis and strokelike episodes (MELAS).
skipped — LLM skipped (--skip-llm)
- ctis·2023-505244-18-01·11·Phase IIa non-randomized open single-arm study, multicentre clinical trial to determine the efficacy and safety of coenzyme Q (Ubiquinol) for patients with mitochondrial disorders and cerebellar ataxias
skipped — LLM skipped (--skip-llm)
- ctis·2024-515129-27-00·Authorised·Assess efficacy of intra-arterial autologous myogenic stam cell therapy for m.3243A>G mutation carriers
skipped — LLM skipped (--skip-llm)
- ctis·2024-515389-15-00·Cancelled·Phase 2b randomized, double-blind, placebo-controlled crossover study evaluating the efficacy and safety of zagociguat in participants with MELAS (PRIZM)
skipped — LLM skipped (--skip-llm)
- ctis·2024-512117-40-00·Authorised·Prospective analysis of the therapeutic efficacy of iron isomaltoside in combination with or without dopaminergic therapy in patients with restless legs syndrome
skipped — LLM skipped (--skip-llm)
- ctis·2024-514377-22-00·Authorised, ongoing·Effect of levothyroxine as adjuvant therapy to a hypocaloric diet in the treatment of obesity: a randomized placebo-controlled trial.
skipped — LLM skipped (--skip-llm)
- ctis·2024-510763-35-00·Authorised, ongoing·An Off-Label Single Arm Clinical Study to Evaluate the Efficacy and Safety of doxecitine and doxribtimine in Adult Subjects with Thymidine Kinase 2 (TK2) Deficiency
skipped — LLM skipped (--skip-llm)
- ctis·2024-514868-11-00·Expired·Effect of Dapagliflozin on myocardial and renal function following aortic valve stenosis intervention
skipped — LLM skipped (--skip-llm)
- ctis·2024-511964-95-00·Authorised, ongoing·Dapagliflozin in the treatment of decompensated liver cirrhosis: phase IIb randomised, controlled clinical trial
skipped — LLM skipped (--skip-llm)
Where to find support
Condition-specific patient organisations, when Orphanet lists them, are on the disease’s Orphanet page. We also link umbrella groups that support undiagnosed and ultra-rare families.
Orphanet entry for WARS2-related combined oxidative phosphorylation defect — check Associations / patient organisations on that page.
India — NPRD
Last verified 2026-07-26This ORPHAcode is not on our curated NPRD list (direct or Mondo-parent match). That does not decide clinical eligibility; families in India should ask a notified Centre of Excellence about current coverage.
Hand-curated for this project. ORPHAcode mappings are best-effort and may be incomplete or imprecise for umbrella categories. Parent (Mondo) matches mean the policy lists a broader category — confirm eligibility with a Centre of Excellence. Financial entitlements summarised from public policy statements and may change. This is not official government guidance.
How we counted this
Europe PMC query (preferred label + any corrected label + Orphanet and Mondo exact synonyms, stoplisted; unioned with resolved MeSH labels when available). UMLS / OMIM / NCIT cross-references are stored on the overview but are not added to the query string.
("WARS2-related combined oxidative phosphorylation defect" OR "Mitochondrial tryptophanyl-tRNA synthetase deficiency" OR "neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures") OR ("WARS2" OR "WARS2 syndrome" OR "WARS2-related")ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):
"WARS2-related combined oxidative phosphorylation defect" OR "Mitochondrial tryptophanyl-tRNA synthetase deficiency" OR "neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures"
Study-type breakdown: 0 interventional · 0 observational · 0 expanded access. Only interventional studies enter the trial headline.
Query health: ok — strategies attempted: phrase; with hits: phrase
Run this search on ClinicalTrials.gov
Confidence reasoning
- Preferred label is multi-word and distinctive
- No synonyms dropped by stoplist
- No label/synonym collisions with other diseases in this corpus
- Publication count (6128) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity
Ingested 2026-07-27T18:33:50.788Z